title: Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model.
abstract: OBJECTIVE
  Although aspiration pneumonitis is a severe complication in patients hospitalized in intensive care units, its pathogenesis is poorly understood. The aim of this study was to determine whether the intensity of lung injury and inflammation developing after aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid.
  
  
  METHODS
  In vitro study on human gastric juice and randomized controlled animal study.
  
  
  METHODS
  Research laboratories of academic institutions.
  
  
  METHODS
  Male New-Zealand white rabbits.
  
  
  METHODS
  Proinflammatory activity of gastric juice from 17 intensive care unit patients and 12 controls undergoing elective surgery was measured based on a target cell activation assay. Two gastric juices from intensive care unit patients with similar pH but differing for their in vitro proinflammatory activity (high and low) were further instilled into the trachea of ventilated rabbits. Lung function, mechanics, pathology, leukocyte infiltration, and local cytokine levels were measured after 6 hrs.
  
  
  RESULTS
  Gastric juice from intensive care unit patients, even buffered at pH 7.4, stimulated human type II-like A549 epithelial cells to up-regulate intercellular adhesion molecule-1 and interleukin-8, significantly more than juice obtained in controls. Gastric juice from an intensive care unit patient supporting high proinflammatory activity in vitro also induced a more severe and persistent drop in PaO2/FIO2 and respiratory system compliance in ventilated rabbits, a worse histologic score, higher lung lavage concentrations of inflammatory cells, interleukin-8 (p < 0.01), and growth-related oncogene-alpha (p < 0.01) than one fluid with low proinflammatory activity.
  
  
  CONCLUSIONS
  Gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high proinflammatory activity is more "toxic" to the lung than one with low proinflammatory activity in a ventilated rabbit model, an effect that is independent of pH and particulate matter content.
authors.affiliation: Laboratoire de Physiopathologie Respiratoire EA 2201, Faculté de Médecine, Université de la Méditerranée, Marseille France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brégeon
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
authors.forename: Stéphane
authors.initials: S
authors.lastname: Delpierre
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Payan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kipson
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pugin
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004731:Endotoxins / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D005750:Gastric Juice / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007362:Intensive Care Units; D007378:Interleukins / Q000502:physiology; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology; D008297:Male; D011015:Pneumonia, Aspiration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D011897:Random Allocation; D012121:Respiration, Artificial; D015656:Respiratory Mechanics; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D004731:Endotoxins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha